Consensus guidelines for the detection of immunogenic cell death

none82siApoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.Kepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G; Cirone, Mara; Colombo, Maria I; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G; Faggioni, Alberto; Formenti, Silvia C; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong-Min; Huang, Xing; Illidge, Tim M; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V; Loi, Sherene; Lowenstein, Pedro R; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean-Ehrland; Riganti, Chiara; Rovere-Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T; Yang, Haining; Zong, Wei-Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, LorenzoKepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G; Cirone, Mara; Colombo, Maria I; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G; Faggioni, Alberto; Formenti, Silvia C; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong Min; Huang, Xing; Illidge, Tim M; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V; Loi, Sherene; Lowenstein, Pedro R; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean Ehrland; Riganti, Chiara; Rovere Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T; Yang, Haining; Zong, Wei Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenz

COVID-19 in Italy. Social Behavior and Governmental Policies

As the COVID-19 crisis began to take shape, all eyes were on Italy, the first Western country to attempt a response to the deadly pandemic. For institutional decision makers and average citizens alike, it was a time of deep uncertainty. As scientists struggled to understand the nature of the virus and how it spread, the gradualness with which information became available caused only deeper uncertainty, as did the inevitable disagreements over which protective actions the government should put in place. Despite some initial delay in its response, the Italian government eventually implemented a nationwide lockdown, which helped control the spread of the disease but simultaneously created unintended consequences for vulnerable populations, like small business owners, women, the elderly, and workers living paycheck to paycheck. Drawing on data surveys conducted during the transition between the first lockdown and staged reopening, this book examines people's risk perception and their willingness to trust the sources and channels of the information that were available to them. It also looks at their attitudes toward the protective behaviors they were asked to adopt, and the ways in which their own cultural worldviews impacted their support for pandemic response policies. With remarkable depth and candor, respondents reflected on what a post-COVID-19 Italy might look like, filling out the book with the hopes and fears of real people who had stared death and the face and lived to tell about it. The book looks ahead to possibilities for future research, policy, and practice. COVID-19 in Italy elaborates and tests several aspects of the Protective Action Decision Model (PADM) in the Italian context, introducing the concept of ontological security and insecurity as an explanatory change factor to help interpret the Italian experience of responding to COVID-19

Doing Web Surveys During Uncertain Times: Reflections From a Research Experience on the COVID-19 Pandemic in Italy

The chapter will focus on using a web survey administered using social networks as a gathering point to collect data on people's risk perception and their undertaking of protective behaviors during the Italian COVID-19 crisis. This was an unprecedented moment in the digital age when there was no possibility of physical contact due to the limitations imposed on coexistence by the health emergency to stem the spread of the virus. This is when digital connections are the only link among people, and the only tool that can be used for doing social research is trying to satisfy the desire for knowledge without limiting the potential for knowledge production even in times of profound uncertainty and several limitations. Analyzing the participants' feedback on web surveys during times of deep uncertainty allows the authors to show what is clearly happening to social research currently. The discussions will be supported by an auto-ethnography conducted on comments left by the respondents to the survey

COVID-19 in Italy. Social Behavior and Governmental Policies.

As the COVID-19 crisis began to take shape, all eyes were on Italy, the first Western country to attempt a response to the deadly pandemic. For institutional decision makers and average citizens alike, it was a time of deep uncertainty. As scientists struggled to understand the nature of the virus and how it spread, the gradualness with which information became available caused only deeper uncertainty, as did the inevitable disagreements over which protective actions the government should put in place. Despite some initial delay in its response, the Italian government eventually implemented a nationwide lockdown, which helped control the spread of the disease but simultaneously created unintended consequences for vulnerable populations, like small business owners, women, the elderly, and workers living paycheck to paycheck. Drawing on data surveys conducted during the transition between the first lockdown and staged reopening, this book examines people's risk perception and their willingness to trust the sources and channels of the information that were available to them. It also looks at their attitudes toward the protective behaviors they were asked to adopt, and the ways in which their own cultural worldviews impacted their support for pandemic response policies. With remarkable depth and candor, respondents reflected on what a post-COVID-19 Italy might look like, filling out the book with the hopes and fears of real people who had stared death and the face and lived to tell about it. The book looks ahead to possibilities for future research, policy, and practice. COVID-19 in Italy elaborates and tests several aspects of the Protective Action Decision Model (PADM) in the Italian context, introducing the concept of ontological security and insecurity as an explanatory change factor to help interpret the Italian experience of responding to COVID-19

il futuro dell'estetica

Forse, l'arte di una volta, l'arte "alta" e tradizionale che ha finito per generare dal proprio interno l'utopia, dell'anti-arte, è finita: nel nostro senso comune ne rimangono alcuni resti, importanti, che però talvolta si contraddicono a vicenda. Ma ciò non significa che non vi siano, sotto tutto ciò, strati più duraturi, utilmente indagabili in sede filosofica. Dopo l'implosione della filosofia dell'arte importata dall'implosione del suo oggetto, il futuro starà allora in un'analisi ontologica, spregiudicata, dell'estetico. Perciò l'estetica, intesa come ombra della filosofia dell'arte, gode e godrà di ottima salute. Quando si sono riconnesse, negli ultimi anni estetica e filosofia dell'arte si sono dimostrate entrambe vivaci, occupandosi di questioni teoriche di cui è possibile immaginare uno sviluppo; ed è certamente un fatto che i risultati così prodotti siano stati messi a disposizione delle altre discipline filosofiche. Ancora una volta, è incoraggiante notare come la comunità scientifica italiana abbia saputo cogliere i segni di questo nuovo corso. In una parola, il futuro dell'estetica - italiana e non solo - sta qui. Questo fascicolo raccoglie gli atti del convegno "il futuro dell'estetica. In onore di Arthur C. Danto", tenutosi a Torino il 3 e il 4 ottobre 2007. I lavori sono stati preceduti dal conferimento della Laurea magistrale honoris causa in Filosofia e Storia delle idee di Arthur Coleman Danto, uno dei massimi esponenti dell'estetica di orientamento analitico: un riferimento imprescindibile per chiunque decida di misurarsi tanto con l'estetica, quanto con la filosofia dell'arte

Flood Disaster Subcultures in the Netherlands: the Parishes of Borgharen and Itteren

The Netherlands knows a persistent threat of flooding. To adapt to this dangerous reality, the Dutch have cultivated what disaster research literature has labeled ‘disaster subcultures’ or a set of cultural (tangible and intangible) tools to deal with the recurrent hazard. While there is abundant attention for the way the Dutch ‘coastal’ and ‘low-lying’ communities deal with the recurrent threat of (coastal) flooding, less is known about the way the Dutch ‘high-lands’ deal with the yearly threat of (fluvial) flooding. This article presents the findings of an explorative research endeavor (2011–2013) aimed at discerning if the disaster subculture concept has contemporary relevance in the Netherlands, particularly with respect to flooding, and if so, whether applying this lens would reveal more about the nature of existing disaster subcultures. Because less is known about the Dutch ‘high-lands,’ we chose to look into the existence and attributes of disaster subcultures in the parishes Borgharen and Itteren, which experience a systematic threat of flooding. Our findings suggest that the disaster subculture lens is valuable as it enables the empirical appreciation of disaster subcultures, even in a small country like the Netherlands, and it unveiled elements of these neighboring parishes’ flood reality that otherwise might have gone unnoticed and that seem central to understanding these two parishes’ levels of vulnerability and resilience. It is our contention that the concept ‘disaster subculture’ makes a greater understanding possible of the cultural context from which vulnerability and resilience to specific and recurrent threats emerge

CONVERGE COVID-19 Working Groups for Public Health and Social Sciences Research - Research Agenda-Setting Paper

This paper was written to help advance convergence-oriented research in the hazards and disaster field. It highlights areas where additional research could contribute new knowledge to the response to and recovery from the pandemic and other disasters yet to come. Questions about the research topics and ethical and methodological issues highlighted here should be directed to the authors who contributed to this paper

ENUBET: A monitored neutrino beam for high precision cross section measurements

International audienceThe main source of systematic uncertainty on neutrino cross section measurements at the GeV scale is represented by the poor knowledge of the initial flux. The goal of cutting down this uncertainty to 1% can be achieved through the monitoring of charged leptons produced in association with neutrinos, by properly instrumenting the decay region of a conventional narrow-band neutrino beam. Large angle muons and positrons from kaons are measured by a sampling calorimeter on the decay tunnel walls (tagger), while muon stations after the hadron dump can be used to monitor the neutrino component from pion decays. This instrumentation can provide a full control on both the muon and electron neutrino fluxes at all energies. Furthermore, the narrow momentum width (<10%) of the beam provides a O(10%) measurement of the neutrino energy on an event by event basis, thanks to its correlation with the radial position of the interaction at the neutrino detector. The ENUBET project has been funded by the ERC in 2016 to prove the feasibility of such a monitored neutrino beam and is cast in the framework of the CERN neutrino platform (NP06) and the Physics Beyond Colliders initiative. In our contribution, we summarize the ENUBET design, physics performance and opportunities for its implementation in a timescale comparable with next long baseline neutrino experiments